Search

Your search keyword '"Howell, L"' showing total 5 results
Start Over Author "Howell, L" Topic phosphorylation
5 results on '"Howell, L"'

4. Activation of G551D CFTR channel with MPB-91: regulation by ATPase activity and phosphorylation.

Author

Derand, Renaud, Bulteau-Pignoux, Laurence, Mettey, Yvette, Zegarra-Moran, Olga, Howell, L. Daniel, Randak, Christoph, Galietta, Luis J.V., Cohn, Jonathan A., Norez, Caroline, Romio, Leila, Vierfond, Jean-Michel, Joffre, Michel, and Becq, Frederic

Subjects
*ADENOSINE triphosphate, *PHOSPHORYLATION, *CYSTIC fibrosis
Abstract

Examines the use of adenosine triphosphatase (ATPase) activity and phosphorylation in the activation of G551D cystic fibrosis transmembrane conductance regulator (CFTR) channel with 5-butyl-6-hydroxy-10-chlorobenzo[c]quinolizinium chloride (MPB 91). Effect of MPB on ATPase; Development of CFTR modulators.

Published
2001

5. Activation of G551D CFTR channel with MPB-91: Regulation by ATPase activity and phosphorylation

Author

L. Daniel Howell, Jonathan A. Cohn, Christoph Randak, Yvette Mettey, Caroline Norez, Renaud Dérand, Laurence Bulteau-Pignoux, Michel Joffre, Frédéric Becq, Jean Michel Vierfond, Luis J. V. Galietta, Leila Romio, Olga Zegarra-Moran, Dérand, R, Bulteau-Pignoux, L, Mettey, Y, Zegarra-Moran, O, Howell, L D, Randak, C, Galietta, L J, Cohn, J A, Norez, C, Romio, L, Vierfond, J M, Joffre, M, and Becq, F

Subjects
Adenosine Triphosphatase, congenital, hereditary, and neonatal diseases and abnormalities, Patch-Clamp Techniques, Physiology, ATPase, Chloride Channel, Enzyme Activator, Patch-Clamp Technique, Thyroid Gland, Enzyme Activators, Cystic Fibrosis Transmembrane Conductance Regulator, CHO Cells, Cystic fibrosis, Chloride Channels, Cricetinae, Gene expression, medicine, Animals, Phosphorylation, Protein kinase A, Ion transporter, Adenosine Triphosphatases, chemistry.chemical_classification, Iodide, biology, Animal, Cell Biology, Iodides, medicine.disease, Cystic fibrosis transmembrane conductance regulator, Rats, Inbred F344, Rats, Cell biology, Electrophysiology, Enzyme, chemistry, Biochemistry, CHO Cell, Quinolizine, biology.protein, Rat, Quinolizines
Abstract

We have designed and synthesized benzo[c]quinolizinium derivatives and evaluated their effects on the activity of G551D cystic fibrosis transmembrane conductance regulator (CFTR) expressed in Chinese hamster ovary and Fisher rat thyroid cells. We demonstrated, using iodide efflux, whole cell patch clamp, and short-circuit recordings, that 5-butyl-6-hydroxy-10-chlorobenzo[c]quinolizinium chloride (MPB-91) restored the activity of G551D CFTR (EC50= 85 μM) and activated CFTR in Calu-3 cells (EC50= 47 μM). MPB-91 has no effect on the ATPase activity of wild-type and G551D NBD1/R/GST fusion proteins or on the ATPase, GTPase, and adenylate kinase activities of purified NBD2. The activation of CFTR by MPB-91 is independent of phosphorylation because 1) kinase inhibitors have no effect and 2) the compound still activated CFTR having 10 mutated protein kinase A sites (10SA-CFTR). The new pharmacological agent MPB-91 may be an important candidate drug to ameliorate the ion transport defect associated with CF and to point out a new pathway to modulate CFTR activity.

Catalog

Books, media, physical & digital resources
See catalog results